3-66220897-C-G

Position:

• chr3-66220897-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_173471.4(SLC25A26):​c.-198C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 632,664 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (17 hom.)
• Consequence: SLC25A26 NM_173471.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830

Genes affected

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-66220897-C-G is Benign according to our data. Variant chr3-66220897-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1315924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A26	NM_001164796.1	c.-305C>G		5_prime_UTR_variant	1/9
SLC25A26	NM_001350993.1	c.-549C>G		5_prime_UTR_variant	1/11
SLC25A26	NM_173471.4	c.-198C>G		5_prime_UTR_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A26	ENST00000676754.1	c.-198C>G		5_prime_UTR_variant	2/11			P1
SLC25A26	ENST00000686511.1	c.-232+39C>G		intron_variant
SLC25A26	ENST00000690634.1	c.-232+39C>G		intron_variant, NMD_transcript_variant
SLC25A26	ENST00000689520.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00501 AC: 763 AN: 152238 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00224 AC: 1078 AN: 480310 Hom.: 17 Cov.: 5 AF XY: 0.00205 AC XY: 534 AN XY: 259904

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000957

Gnomad4 FIN exome AF: 0.0000617

Gnomad4 NFE exome AF: 0.000311

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.00506 AC: 771 AN: 152354 Hom.: 14 Cov.: 33 AF XY: 0.00507 AC XY: 378 AN XY: 74498

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00596 Hom.: 3

Bravo AF: 0.00592

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.5
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs370822424; hg19: chr3-66271323;